Cancer of the uterine cervix is the second most common cancer in women world-wide and is responsible for approximately 250,000 cancer deaths a year.
Cervical cancer development is characterized by a sequence of premalignant lesions, so called cervical intraepithelial neoplasia (CIN), which are graded I to III, referring to mild dysplasia (CIN I), moderate dysplasia (CIN II) and severe dysplasia/carcinoma in situ (CIN III). CIN I is also referred to as low grade squamous intraepithelial lesion (LSIL) and CIN II and CIN III together as high grade squamous intraepithelial lesion (HSIL).
Over the past decade it has been well established that cervical carcinogenesis is initiated by an infection with high-risk human papillomavirus (HPV). Expression of the viral oncogenes E6 and E7, which disturb the p53 and Rb tumor suppressor pathways, respectively, has been shown to be essential for both the onset of oncogenesis and the maintenance of a malignant phenotype. However, consistent with a multistep process of carcinogenesis, additional alterations in the host cell genome are required for progression of an hr-HPV infected cell to an invasive carcinoma.
In line with multiple events underlying cervical carcinogenesis is the observation that only a small proportion of women infected with high-risk HPV will develop high-grade premalignant cervical lesions (CIN III) or cervical cancer, and in most women with premalignant cervical lesions the lesions regress spontaneously.
However, at present no markers exist to predict which premalignant lesions will regress or ultimately progress to cervical cancer. Therefore, general medical practice comprises the treatment of all women with morphologically confirmed CIN II and CIN III, in order to prevent the development of cervical cancer. Consequently, many women are unnecessarily treated and unnecessarily worried.